Artemisinin suppresses hepatocellular carcinoma cell growth, migration and invasion by targeting cellular bioenergetics and Hippo-YAP signaling

Autor: Lu Wang, Naxin Liu, Pingyi Chen, Bin Lu, Mingyue Yang, Jing Lu, Shengnan Han, Yongzhang Liu, Qiumei Jin, Yujie Li, Qin Chen, Fugen Shangguan, Hua Shao, Mingming Fei
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Carcinoma
Hepatocellular
Health
Toxicology and Mutagenesis
Mice
Nude
010501 environmental sciences
Mitochondrion
Biology
Protein Serine-Threonine Kinases
Toxicology
01 natural sciences
03 medical and health sciences
In vivo
Cell Movement
Cell Line
Tumor
medicine
Animals
Humans
Hippo Signaling Pathway
Neoplasm Invasiveness
Artemisinin
0105 earth and related environmental sciences
Adaptor Proteins
Signal Transducing
Cell Proliferation
Cell growth
Liver Neoplasms
Cell migration
YAP-Signaling Proteins
General Medicine
medicine.disease
Antineoplastic Agents
Phytogenic
Xenograft Model Antitumor Assays
digestive system diseases
In vitro
Artemisinins
030104 developmental biology
Hepatocellular carcinoma
Cancer research
Signal transduction
medicine.drug
Signal Transduction
Transcription Factors
Zdroj: Archives of toxicology. 93(11)
ISSN: 1432-0738
Popis: The primary liver cancer (PLC) is one of the leading causes of cancer-related death worldwide. The predominant form of PLC is hepatocellular carcinoma (HCC), which accounts for about 85% of all PLC. Artemisinin (ART) was clinically used as anti-malarial agents. Recently, it was demonstrated to inhibit cell growth and migration in multiple cancer types. However, the molecular mechanism underlying these anti-cancer activity remains largely unknown. Herein, it is discovered that ART dramatically suppresses HCC cell growth in vitro through arresting cell cycle progression, and represses cell migration and invasion via regulating N-cadherin-Snail-E-cadherin axis. In addition, the disruption of cellular bioenergetics contributed to ART-caused cell growth, migration and invasion inhibition. Moreover, ART (100 mg/kg, intraperitoneally) substantially inhibits HCC xenograft growth in vivo. Importantly, Hippo-YAP signal transduction is remarkably inactivated in HCC cells upon ART administration. Collectively, these data reveal a novel mechanism of ART in regulating HCC cell growth, migration, and invasion, which indicates that ART could be considered as a potential drug for the treatment of HCC.
Databáze: OpenAIRE
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